ABSTRACT Despite well-documented effects on families from parenting interventions aimed at improving child school readiness for low-income families, making progress at the population level has been limited. Key barriers include identification and engagement of families, challenges of scalability and sustainability at low cost within existing service systems, and heterogeneity of risk even in high-risk populations. Vulnerability in parent-child relational health is linked to detriments in child school readiness; however, such vulnerabilities have yet to be systematically integrated into population-level strategies, contributing to limitations in population-level progress. The Smart Beginnings (SB) model (R01HD076390-05) is a birth to 3 year program that addresses each of these barriers through: 1) utilization of pediatric primary care as a universal platform to facilitate population- level engagement and scalability; 2) provision of a tiered preventive intervention through universal primary prevention (Video Interaction Project [VIP], delivered through health care) integrated with a selective, targeted secondary intervention (Family Check Up [FCU], delivered through strategic home visiting). A significant innovation of the SB approach is its use of periodic, systematic screening for early parent-child relational health risks to inform targeted delivery of support for parenting by addressing ecological and proximal stressors. Both of the interventions integrated in SB (VIP and FCU) bring an established record of sustained impact for low-income families. Our current study (including program delivery and assessment through child age 2 years) examines the impact of the integrated model in a randomized controlled trial (RCT) of 400 families in a scalable platform: pediatric primary care. Preliminary findings with initial outcomes through age 2 demonstrate substantial promise, with positive impacts on relational health (enhanced parenting of infants/toddlers) and child development (reduced toddler problem behaviors), paving the way for enhanced later school readiness. The current proposal seeks to build on this work, by completing delivery of the SB model through child age 3 and performing assessments of children in the RCT at ages 4 and 6 years to determine whether early impacts of the SB tiered intervention on relational health and early child development translate to later benefits for school readiness. In addition, the proposal will address important gaps necessary for refinement and implementation of tiered prevention models like SB including: 1) understanding mechanisms of action (i.e., mediation) of SB across all families and by intervention offer, and 2) moderation of treatment response based on baseline differences in financial/human capital and psychosocial risk. Findings from the application will provide a long-term test of program efficacy with information to support next-stage scaling. Completion of study aims will directly support NICHD priorities seeking to optimize school readiness skills in economically and socially disadvantaged children and could result in transformative changes in policy and practice.